Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women,Nature Communications

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Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women
Nature Communications ( IF 16.6 ) Pub Date : 2020-11-25 , DOI: 10.1038/s41467-020-19733-6
Valgerdur Steinthorsdottir ₁ , Ralph McGinnis ₂ , Nicholas O Williams ₂ , Lilja Stefansdottir ₁ , Gudmar Thorleifsson ₁ , Scott Shooter ₂ , João Fadista _{3,

4} , Jon K Sigurdsson ₁ , Kirsi M Auro ₅ , Galina Berezina ₆ , Maria-Carolina Borges _{7,

8} , Suzannah Bumpstead ₂ , Jonas Bybjerg-Grauholm ₉ , Irina Colgiu ₂ , Vivien A Dolby ₁₀ , Frank Dudbridge ₁₁ , Stephanie M Engel ₁₂ , Christopher S Franklin ₂ , Michael L Frigge ₁ , Yr Frisbaek ₁₃ , Reynir T Geirsson ₁₃ , Frank Geller ₃ , Solveig Gretarsdottir ₁ , Daniel F Gudbjartsson _{1,

14} , Quaker Harmon ₁₅ , David Michael Hougaard ₉ , Tatyana Hegay ₁₆ , Anna Helgadottir ₁ , Sigrun Hjartardottir ₁₃ , Tiina Jääskeläinen ₁₇ , Hrefna Johannsdottir ₁ , Ingileif Jonsdottir _{1,

18} , Thorhildur Juliusdottir ₁ , Noor Kalsheker ₁₉ , Abdumadjit Kasimov ₁₆ , John P Kemp _{7,

20} , Katja Kivinen ₂₁ , Kari Klungsøyr _{22,

23} , Wai K Lee ₂₄ , Mads Melbye _{3,

25,

26} , Zosia Miedzybrodska ₂₇ , Ashley Moffett ₂₈ , Dilbar Najmutdinova ₂₉ , Firuza Nishanova ₂₉ , Thorunn Olafsdottir _{1,

18} , Markus Perola _{5,

30} , Fiona Broughton Pipkin ₃₁ , Lucilla Poston ₃₂ , Gordon Prescott _{27,

33} , Saedis Saevarsdottir ₁ , Damilya Salimbayeva ₆ , Paula Juliet Scaife ₃₁ , Line Skotte ₃ , Eleonora Staines-Urias ₁₁ , Olafur A Stefansson ₁ , Karina Meden Sørensen ₃₄ , Liv Cecilie Vestrheim Thomsen _{35,

36} , Vinicius Tragante _{1,

37} , Lill Trogstad ₃₈ , Nigel A B Simpson ₃₉ , , , Tamara Aripova ₁₆ , Juan P Casas _{40,

41} , Anna F Dominiczak ₂₄ , James J Walker ₁₀ , Unnur Thorsteinsdottir _{1,

18} , Ann-Charlotte Iversen ₃₆ , Bjarke Feenstra ₃ , Deborah A Lawlor _{7,

8,

42} , Heather Allison Boyd ₃ , Per Magnus ₄₃ , Hannele Laivuori _{17,

44,

45} , Nodira Zakhidova ₁₆ , Gulnara Svyatova ₆ , Kari Stefansson _{1,

18} , Linda Morgan ₁₉

Affiliation

deCODE genetics/Amgen Inc., Reykjavik, Iceland.
Wellcome Sanger Institute, Cambridge, UK.
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden.
Finnish Institute for Health and Welfare, Helsinki, Finland.
Scientific Center of Obstetrics, Gynecology and Perinatology, Almaty, Kazakhstan.
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
Department for Congenital Disorders, Danish Centre for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark.
Leeds Institute of Medical Research (LIMR), School of Medicine, University of Leeds, Leeds, UK.
Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, NC, USA.
Institute of immunology and human genomics, Uzbek Academy of Sciences, Tashkent, Uzbekistan.
Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
School of Life Sciences, University of Nottingham, Nottingham, UK.
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Division of Applied Medicine, School of Medicine, Medical Sciences, Nutrition and Dentistry, University of Aberdeen, Aberdeen, UK.
Department of Pathology, University of Cambridge, Cambridge, UK.
Republic Specialized Scientific Practical Medical Centre of Obstetrics and Gynecology, Tashkent, Uzbekistan.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
School of Medicine, University of Nottingham, Nottingham, UK.
Department of Women and Children's Health, King's College London, London, UK.
Lancashire Clinical Trials Unit, University of Central Lancashire, Preston, UK.
The Danish National Biobank, Statens Serum Institut, Copenhagen, Danmark.
Department of Clinical Science, Centre for Cancer Biomarkers CCBIO, University of Bergen, Bergen, Norway.
Department of Clinical and Molecular Medicine, Centre of Molecular Inflammation Research (CEMIR), Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Department of Infectious Disease Epidemiology and Modelling, Norwegian Institute of Public Health, Oslo, Norway.
Division of Womens and Children's Health, School of Medicine, University of Leeds, Leeds, UK.
Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Bristol NIHR Biomedical Research Centre, Bristol, UK.
Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland.
Department of Obstetrics and Gynecology, Tampere University Hospital and Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland.

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.

中文翻译：

高血压的遗传易感性与欧洲和中亚女性的先兆子痫有关

先兆子痫是一种严重的妊娠并发症，影响母体和胎儿的健康。在对欧洲和中亚母亲的全基因组关联荟萃分析中，我们在ZNF831 /20q13 和FTO /16q12 的母体基因组中鉴定了与先兆子痫相关的序列变异。这些是先前建立的血压 (BP) 变体，FTO变体也与体重指数 (BMI) 相关。对 BP 变体的进一步分析确定MECOM /3q26、FGF5 /4q21 和SH2B3的变体/12q24 还通过母体基因组与先兆子痫相关。我们进一步表明，高血压的多基因风险评分与先兆子痫有关。然而，与妊娠期高血压的比较表明，其他因素会改变先兆子痫的风险。

更新日期：2020-11-26

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